- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01601821
Open Label Comparative Study Of De Novo Renal Allograft Recipients Receiving CSA + MMF + Corticosteroids Versus CSA + Rapamune + Corticosteroids
November 15, 2018 updated by: Pfizer
An Open Label Comparative Study Of De Novo Renal Allograft Recipients Receiving CSA + MMF + Corticosteroids Versus CSA + Rapamune + Corticosteroids With Further CSA Elimination In The Rapamune Arm With The Introduction Of MMF
To compare the safety and efficacy of cyclosporine (CsA) + mycophenolate mofetil (MMF) + corticosteroids © to CsA + Rapamune + Cs with CsA elimination in the Rapamune arm with the introduction of MMF in de novo renal allograft recipients.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
245
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
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Tehran, Iran, Islamic Republic of
- Modarres Hospital
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Tehran, Iran, Islamic Republic of
- Shariati Hospital
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Tehran, Iran, Islamic Republic of
- Taleqani Hospital
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Tehran, Iran, Islamic Republic of
- Labbafinejad Hospital
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
13 years to 18 years (ADULT, CHILD)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Age 13 years and weight 40 kg
- End-stage renal disease, with patients receiving a primary or secondary renal allograft from a living-unrelated donor, or from a living-related donor.
- Women who are of childbearing potential must have a negative pregnancy test before enrollment in the study and agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months following discontinuation from the study.
- Total white blood cell count 4.0 x 109/L (4,000/mmP3P), platelet count 100 x 10P9P/L(100,000/mmP3P), fasting triglycerides ≤ 4.6 mmol/L (400 mg/dL), fasting cholesterol ≤ 7.8 mmol/L (300 mg/dL). If it is not possible to obtain fasting triglycerides and cholesterol before surgery, historical values (within 1 year) may be used.
- Signed and dated informed consent (parent or legal guardian must provide consent for patients <18 years of age). An assent form will be signed by patients < 18 years of age enrolled in the study.
Exclusion Criteria:
- Evidence of active systemic or localized major infection at the time of initial Sirolimus administration.
- Cadaveric donors
- History of malignancy within 5 years before enrollment into the study (with the exception of adequately treated basal cell or squamous cell carcinoma of the skin)
- Use of any investigational drug other than specified in the protocol during the 4 weeks before enrolling in the study.
- Use of planned antibody induction therapy at the time of transplantation.
- Active gastrointestinal disorder that may interfere with drug absorption.
- Known hypersensitivity to Sirolimus, MMF or Cyclosporine or its derivatives.
- Multiple organ transplants (2 or more organ transplant e.g. Kidney and Pancreas).
- Patient with high risk of rejection (eg. Patients with a PRA >50%, black patients and patients with 2nd transplant who lost their first graft within the first 6 months).
- Evidence of infiltrate, cavitation, or consolidation on chest x-ray obtained during pre-study screening
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Arm A (CsA+Rapamune+CS)
|
Part 1: Rapamune will be given as a loading dose of 6 mg once followed by maintenance dose of 2 mg to achieve a target trough level of 8-15 ng/ml.
Part 2: Rapamune dose will be adjusted to achieve a target trough level of 10-15ng/ml through 6 months
|
EXPERIMENTAL: Arm B (CsA+MMF+CS)
|
The control arm is the standard local practice (official protocol) in Iran: Cyclosporine + MMF + Corticosteroid. The time period is from pre-study screening / baseline evaluation up to 12 months for patients who are maintained on CsA + MMF + CS. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Efficacy Failure
Time Frame: Baseline up to Month 12
|
Efficacy failure was defined as first occurrence of either biopsy confirmed acute rejection, graft loss or death within 12 months of post-transplantation. Percentage of participants with efficacy failure was reported.
|
Baseline up to Month 12
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Serum Creatinine Level
Time Frame: Month 3, 6, 12
|
Serum creatinine is an indicator of kidney function.
Creatinine is a substance formed from the metabolism of creatine, commonly found in blood, urine and muscle tissue.
It is removed from the blood by the kidneys and excreted in urine.
An increased level of creatinine in the blood indicates decreased kidney function.
Normal adult blood levels of creatinine are 0.5 to 1.1 milligram per deciliter (mg/dL) for females and 0.6 to 1.2 mg/dL for males; however, the normal values are age-dependent as elderly patients typically have smaller muscle mass.
|
Month 3, 6, 12
|
Creatinine Clearance
Time Frame: Month 3, 6, 12
|
Creatinine clearance (CCr) is a measure of kidney function.
CCr is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time.
Normal values for healthy, young males are in the range of 100-135 millimeters per minute (mL/min) and for females, 90-125 mL/min.
Creatinine clearance decreases with age.
A low creatinine clearance rate indicates poor kidney function.
|
Month 3, 6, 12
|
Glomerular Filtration Rate (GFR) by Nankivell Method
Time Frame: Month 3, 6, 12
|
GFR is an index of kidney function.
GFR describes the flow rate of filtered fluid through the kidney.
GFR was calculated using the Nankivell formula.
GFR by Nankivell equation= (6.7 per serum creatinine) plus (0.25*body weight) minus (0.5*serum urea) minus (100 per height square) plus (35 for male or 25 for female).
A normal GFR is greater than (>)90 mL/min per 1.73 m^2 [mL/min/1.73
m^2], although children and older people usually have a lower GFR.
Lower values indicated poor kidney function.
A GFR less than (<)15 mL/min/1.73
m^2 indicated kidney failure.
|
Month 3, 6, 12
|
Incidence of Biopsy-Confirmed Acute Rejection
Time Frame: Baseline up to Month 6
|
Diagnosis of acute rejection was made via kidney biopsy using Banff criteria.
Percentage of participants with biopsy-confirmed acute rejection was reported.
|
Baseline up to Month 6
|
Histologic Grade of First Acute Rejection
Time Frame: Baseline up to Month 12
|
Diagnosis of acute rejection was made via kidney biopsy.
Categorization of biopsies with suspected acute rejection was based on histological findings using updated 1997 Banff criteria.
Grade 1A: cases with significant interstitial infiltration (>25% of parenchyma affected) and foci of moderate tubulitis (5-10 cells/tubular cross section), Grade 1B: with severe tubulitis (>10 cells/tubular cross section), Grade 2A: mild-moderate intimal arteritis, Grade 2B: severe intimal arteritis and Grade 3: transmural arterits and/or fibrinoid necrosis.
Data is reported as percentage of participants.
|
Baseline up to Month 12
|
Percentage of Participants Who Survived
Time Frame: Month 12
|
Survival defined as participants living with or without a functioning graft.
|
Month 12
|
Percentage of Participants With Graft Survival
Time Frame: Month 12
|
Graft survival defined as those participants who did not experience graft loss.
Graft loss defined as physical loss (nephrectomy), functional loss (necessitating maintenance dialysis for >8 weeks), retransplant or death during the first 12 months after randomization.
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Month 12
|
Incidence of Presumptive or Documented Infection
Time Frame: Baseline up to Month 12
|
Presumptive or documented infection during the 12 months after transplantation; was confirmed by culture, biopsy, or serology and reported.
Percentage of participants with presumptive or documented infection was reported.
|
Baseline up to Month 12
|
Incidence of Histologically Confirmed Lymphoproliferative Disease
Time Frame: Baseline up to Month 12
|
Lymphoproliferative disorder represents an abnormal proliferation of B cells in response to either primary or reactivated infection with Epstein-Barr virus.
Percentage of participants with histologically confirmed lymphoproliferative disease was reported.
|
Baseline up to Month 12
|
Percentage of Participants With Efficacy Failure or Premature Elimination
Time Frame: Month 12
|
Efficacy failure was defined as the first occurrence of acute rejection, graft loss, or death.
Premature elimination was defined as elimination from the study for any other reason.
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Month 12
|
Incidence of Anemia
Time Frame: Baseline up to Month 12
|
Diagnostic criterion for anemia was based on the laboratory results; in men: hemoglobin (Hb) <14 gram per deciliter (g/dL), hematocrit (Hct) <42%, or red blood cells (RBCs) <4.5 million/liter (million/L); for women: Hb <12 g/dL, Hct <37%, or RBC < 4 million/L.
Percentage of participants with anaemia was reported.
|
Baseline up to Month 12
|
Number of Participants Who Discontinued
Time Frame: Month 12
|
Number of participants who discontinued the study treatment due to any reason is reported.
|
Month 12
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
April 1, 2006
Primary Completion (ACTUAL)
March 1, 2008
Study Completion (ACTUAL)
March 1, 2008
Study Registration Dates
First Submitted
May 3, 2012
First Submitted That Met QC Criteria
May 16, 2012
First Posted (ESTIMATE)
May 18, 2012
Study Record Updates
Last Update Posted (ACTUAL)
December 12, 2018
Last Update Submitted That Met QC Criteria
November 15, 2018
Last Verified
November 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 0468H-102012
- B1741220
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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